Interaction of genetic and environmental factors regulating the local immune response is being studied, especially the influence of neonatal exposure to bacterial antigen by various routes on the development of salivary antibody. The model system used is based on our published observations that inbred Harvard caries-resistant (HCR) rats differ from the Harvard caries-susceptible (HCS) rats in their immune response to cariogenic Streptococcus faecalis ND 547 (S.f.). We are exploring the environmental variables that appear to influence this difference to identify a factor regulating antibody production in the gnotobiotic HCR rat. Dental caries incidence appears to correlate well with changes in bacterial agglutinin titer, induced by mucosal associated antigens in this model. Responses to S. mutans will be compared with those to S.f. and to oral immunization studies reported in similar rat model systems. Identification of immunoglobulin classes of specific antibody should help to define further the observed differences in response and the possible protective function of secretory antibody and the local immune response.